Investigation of miRNAs Associated with Inflammation and Apoptosis in Patients with Idiopathic Trigeminal Neuralgia

Background: Trigeminal neuralgia (TN) is a severe neuropathic pain disorder primarily diagnosed on clinical grounds, and objective molecular biomarkers that could support diagnosis remain limited. Increasing evidence suggests that inflammation-apoptosis interactions contribute to TN pathophysiology. Methods: In this exploratory prospective case-control study, circulating apoptosis-related microRNAs (miRNAs) were analyzed in 30 patients with idiopathic TN and 20 healthy controls. Plasma miRNA expression levels were quantified using quantitative real-time polymerase chain reaction. Diagnostic performance of individual miRNAs was assessed using receiver operating characteristic (ROC) curve analysis. A multivariable logistic regression model integrating multiple miRNAs was constructed to evaluate combined diagnostic performance, with internal validation performed using five-fold cross-validation. Results: Circulating miRNA expression profiles differed between TN patients and controls. Among individual markers, hsa-miR-183-5p demonstrated the highest diagnostic accuracy (AUC = 0.72), followed by hsa-miR-23a-3p (AUC = 0.65). hsa-miR-223-3p showed reversed directionality (AUC = 0.28), consistent with lower expression in TN and high specificity but low sensitivity at the optimal threshold. The combined miRNA panel achieved an apparent AUC of 0.86, with a mean cross-validated AUC of 0.84 ± 0.12, suggesting improved discrimination over single miRNAs but with variability consistent with the limited sample size. Conclusions: Apoptosis-related circulating miRNAs exhibit distinct expression patterns in idiopathic TN. While individual miRNAs show modest diagnostic performance, integration into a multi-miRNA panel improved discrimination between TN patients and healthy controls in this pilot dataset. These findings support the potential of apoptosis-based miRNA signatures as candidate minimally invasive biomarkers for TN, warranting further validation in larger, independent cohorts, ideally including clinically relevant disease-control facial pain conditions.